J Cardiol 2007 May; 49（5）: 231 – 239

Association Between Silent ST
Segment Depression in Exercise
Electrocardiography and Insulin
Resistance in Obese Subjects＊1,＊2

Ryoma MICHISHITA, MS＊2,＊3

Naoko SHONO, MD

＊4

Akira

KIYONAGA, MD

Hiroaki

TANAKA, PhD＊4＊4Munehiro SHINDO, MS＊1TakakiKASAHARA, MD

Toshiyuki

TSURUTA, MD

＊1

Teruo

INOUE, MD, FJCC＊2

Koichi

NODE, MD, FJCC

＊2

Abstract ─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
Objectives. This study was designed to clarify the association between ST segment depression in exercise electrocardiography（ECG）and insulin resistance in obese subjects.
Methods. A multistage graded submaximal exercise stress test on the bicycle ergometer was performed（39 men and 75 women, mean age 50.9 ± 12.2
under CM5-lead ECG monitoring in 114 obese subjects.
years, mean body mass index 28.6 ± 3.1 kg/m2）
Results. In 27 patients showing ST segment depression at the final exercise intensities（abnormal ST）,
insulin resistance index by homeostasis model assessment（HOMA-IR）was higher and insulin sensitivity
index was lower than in the remaining 87 patients with normal ST segment level（normal ST）. The abnormal ST group showed significantly higher plasma glucose and serum insulin levels during the oral glucose
tolerance test
（OGTT）than the normal ST group. The abnormal ST group showed a significantly higher
prevalence of hypertension, impaired glucose tolerance and metabolic syndrome than the normal ST group.
Multiple logistic regression analysis showed that insulin resistance as evaluated by fasting insulin, ∑insulin during OGTT, HOMA-IR, insulin sensitivity index, the levels of uric acid, fasting glucose, systolicblood pressure and maximal oxygen uptake were independently associated with ST segment depression.
Conclusions. These results suggest that insulin resistance may involve pathological ST depression during exercise, as well as previously reported factors such as hyperglycemia, hyperuricemia, hypertension
and lower aerobic capacity.
─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────J Cardiol 2007 May; 49（5）: 231−239

Key Words■ Exercise test

■ Insulin■ Ischemia

INTRODUCTION
Insulin resistance or hyperinsulinemia might be■ Obesity■ ST segment

an etiologic cause of obesity, hypertension, type 2
diabetes mellitus, hyperuricemia and arteriosclerosis.1−3）The common association of obesity, hyper-──────────────────────────────────────────────
＊1
医療法人友和会 鶴田運動機能回復クリニック : 〒 849−0305 佐賀県小城市牛津町上砥川 174−8 ; ＊ 2 佐賀大学医学部 循環器・腎臓内科，佐賀 ; ＊ 3 ライフスタイル医科学研究所，福岡 ; ＊ 4 福岡大学スポーツ科学部 運動生理学研究室，福岡＊1
Clinic of Tsuruta Orthopaedic Surgery, Saga ; ＊ 2Department of Cardiovascular and Renal Medicine, Saga University Faculty of
Medicine, Saga ; ＊ 3Institute of Lifestyle Medical Science, Fukuoka ; ＊ 4Department of Exercise Physiology, School of Physical
Education, Fukuoka University, Fukuoka
Address for correspondence : MICHISHITA R, MS, Clinic of Tsuruta Orthopaedic Surgery, Kamitogawa Ushizumachi 174−8, Ogi,
Saga 849−0305 ; E-mail : rheuma.clinic.21@lime.ocn.ne.jp
Manuscript received December 8, 2006 ; revised January 29, 2007 ; accepted February 5, 2007

231

232

Michishita, Shono, Kiyonaga et altension, type 2 diabetes mellitus, hyperuricemia
and arteriosclerosis is thought to be attributable tohyperinsulinemia and insulin resistance. Moreover,some studies indicating the involvement of visceralobesity in atherosclerois and its relationship withinsulin resistance have been reported.2−4）In addition, insulin resistance or hyperinsulinemia is correlated with the incidence of coronary heart disease
5−7）and stroke.5, 8）Several studies9−11）have demonstrated a relationship between abnormal ST-T in
resting 12-lead electrocardiography（ ECG）and
insulin resistance or hyperinsulinemia. However,
the relationship between ST segment depression in
exercise ECG and insulin resistance or hyperinsulinemia is still unknown.
Our hypothesis is that insulin resistance or
hyperinsulinemia may be a sensitive factor for predicting myocardial ischemia during exercise. This
study was designed to clarify the relationshipbetween ST segment depression in exercise ECG
and insulin resistance or hyperinsulinemia as wellas coronary risk factors in obese subjects.
SUBJECTS AND METHODS
Subjects
The subjects consisted of 114 obese subjects, 39
men and 75 women with mean age 50.9 ± 12.2
years and mean body mass index（BMI）28.6 ± 3.1
kg/m2, with coronary risk factors including hypertension, impaired glucose tolerance, hyperlipidemia, hyperuricemia and hyperinsulinemia. All
patients were recruited to participate in our program of exercise therapy for risk factor intervention. Patients taking cardioactive drugs such as antihypertensive drugs, statin and hypoglycemia
agents, patients with a history of angina pectoris or
myocardial infarction, or patients with an abnormal
resting 12-lead ECG were excluded from this study.
There were no patients with left ventricular hypertrophy（RV5 ＋ SV1 ＞− 3.5 mV or RV5 ＞− 2.6 mV on
resting ECG）. The design and methods of thisstudy were approved by the Ethics Committee ofSaga University. Written informed consent was
obtained from each patient after the study design
and the potential risks of the study were explained.
Blood sampling and anthropometric measurements
Blood samples were collected early in the morning by venipuncture from an antecubital vein afterat least 12 hours fasting. Next, the 75 g oral glu-

cose tolerance test（OGTT）was performed to analyze plasma glucose and serum insulin concentration. Blood samples were taken at 30, 60, 90 and
120 min after the administration of an oral glucose
load. High-density lipoprotein cholesterol was measured by the direct method, low-density lipoproteincholesterol, triglyceride and plasma glucose by an
enzymatic method, serum insulin level by the
enzyme immunoassay method, hemoglobin A 1cby the high performance liquid chromatographymethod, and serum uric acid by the uricase peroxidase method, using the fasting blood samples.
The insulin resistance was assessed using fasting
serum insulin,Σ insulin during OGTT and
Matthews s homeostasis model assessment（HOMA-IR）12）based on the following formula :fasting glucose（mg/dl）× fasting insulin（μU/ml）/405. The insulin sensitivity index was calculatedusing a method by Matsuda and DeFronzo13）basedon the following formula : 10,000/square root of（fasting glucose × fasting insulin）×（mean glucose × mean insulin during OGTT）. Hypertension,
impaired glucose tolerance, hyperlipidemia, hyperuricemia and hyperinsulinemia were defined ascoronary risk factors, and the total number of risk
factors was also calculated for each subjects.
Metabolic syndrome was defined according to themetabolic syndrome diagnostic criteria in Japan.14）
BMI was calculated as the ratio of body weight（kg）to height（m2）. The waist circumference wasmeasured at the level of umbilicus. The percentage
body fat, fat mass and lean body mass（LBM）was
measured using the bioelectrical impedance method（HBF-302, OMRON）.
Exercise stress test
Prior to starting the exercise therapy, a multistage
graded submaximal exercise stress test on an electric bicycle ergometer was performed for each subject. The workload was increased by 5 or 10 W
every 4 min, depending on their daily activity level.
The CM5-lead ECG（ML-1800, FUKUDA DENSHI）was recorded continuously during exercise.
The ST segment was automatically measured at
0.04 sec from J point. More than 0.10 mV of horizontal or downslope ST segment depressions wereconsidered to be significant. The following parameters were simultaneously measured at rest and at
the last 1 min of each stage : the rate of perceived
exhaustion, the blood pressure（FB-300, FUKUDADENSHI）, and the blood lactate concentration
J Cardiol 2007 May; 49（5）: 231 – 239

ST Segment Depression and Insulin Resistance（Lactate Pro, ARKRAY）, and were plotted against
the exercise intensities. The workload at the firstbreaking point of the blood lactate level was used
to determine the lactate threshold（LT）. When noclear LT could be obtained, the LT was determinedby the method of Beaver et al.15）The estimated
was determinedmaximal oxygen uptake（・VO2 max）
by the nomogram of Åstrand and Ryhming, 16）
which was measured from heart rate at three different submaximal workloads. The end point of theexercise test（final exercise intensity）was determined on the basis of either achieving 4 mmol/l ofblood lactate concentration or the criteria of theguidelines of the American College of Sports
Medicine.17）

Table 1

Statistical analysis
The data are shown as the mean ± SD. Statisticalanalysis was performed using the StatView software package. The subjects were divided into twogroups, which were defined as patients with andwithout 0.10 mV ST segment depression at the final
exercise intensities（ normal and abnormal ST
groups）. Inter-group comparisons were performed
using the unpaired t-test for continuous variables
and chi-square test for categorical variables. Serialchanges in plasma glucose and serum insulin levels
during OGTT were assessed using repeated measures analysis of variance for intra- and inter-groupcomparisons. Stepwise multiple logistic regression
analysis was performed to determine the association between the ST segment depression at the final
exercise intensities and the coronary risk factors. A

Comparison of patient characteristics between the normal and abnormal ST groups
Normal ST group(n＝87)

Abnormal ST group(n＝27)

p valueMen/women

28/59

11/16

NS

Age（yr）

49.2±12.951.4±12.1

NS

67/20

21/6

NS
NS

Smoking habit（no/yes）
HDL-C（mg/dl）

55.6±11.9

53.3±14.4

LDL-C（mg/dl）

133.4±34.6

140.4±30.1

NS

Triglyceride（mg/dl）

108.6±49.2

164.7±166.5＜0.01

5.2±0.5

5.3±0.6

NS

HbA1c（%）
Fasting glucose（mg/dl）

93.9±11.9

103.0±15.1＜0.01

Fasting insulin（U/ml）

8.4±4.912.6±4.2＜0.01

HOMA-IR1.99±1.25

3.12±1.17＜0.01

Insulin sensitivity index

6.12±3.16

3.51±1.53＜0.01

Uric acid（mg/dl）

5.3±1.3

6.1±1.6＜0.05

2

BMI（kg/m ）28.6±3.428.5±2.7

NS

Percent body fat（%）

34.0±9.1

33.8±9.3

NS

Waist circumference（cm）

89.8±10.992.3±11.0

NS

Resting SBP（mmHg）

121.2±16.6131.0±20.0＜0.05

Resting DBP（mmHg）

79.4±10.4

83.7±12.3

0.07

Resting ST segment（mV）
・VOmax/LBM（ml/min/kg）

0.003±0.028−0.006±0.038

NS43.1±6.2

39.1±3.7＜0.01

LT/body weight（W/kg）

0.79±0.85

0.60±0.20

0.06

Number of risk factors

2.6±1.3

3.5±1.4＜0.05

Continuous values are mean±SD.
Hypertension, impaired glucose tolerance, hyperlipidemia, hyperuricemia and hyperinsulinemia were defined as risk
factors for coronary heart disease, and the total number of risk factors was also calculated for each subject.
HDL-C＝high-density lipoprotein cholesterol ; LDL-C＝low-density lipoprotein cholesterol ; HbAc1＝hemoglobin
A1c; HOMA-IR＝insulin resistance by homeostasis model assessment ; BMI＝body mass index ; SBP＝systolicblood pressure ; DBP＝diastolic blood pressure ; ・VO2max＝maximum oxygen uptake ; LBM＝lean bodymass ; LT＝lactate threshold.

J Cardiol 2007 May; 49（5）: 231 – 239

233

234

Michishita, Shono, Kiyonaga et al

Fig. 1 Plasma glucose（left）and serum insulin（right）
responses during the 75g oral glucose tolerance
test in 87 patients with normal ST segment（normal ST group）
and 27 patients with exerciseinduced ST segment depression（abnormal ST group）
The results are shown as the mean ± SD. ＊ p ＜ 0.05, ＊＊ p ＜ 0.01.

probability value of less than 0.05 was considered
to be statistically significant.
RESULTSST segment depression at the final exercise
intensities was observed in 27/114 patients（23.7%）. However, ST segment depression wasobserved in none of these 27 patients before theexercise reached LT level. There were no significant differences in sex, age and smoking habit
between normal and abnormal ST groups. The
maximum heart rate increase at the final exercise
intensities was 72.6 ± 6.1%（maximum heart rate
, which showed no sigwas calculated by 220−age）
nificant differences between the normal and abnormal ST groups（72.4 ± 6.3% vs 73.4 ± 5.3%）. The
blood lactate concentration at the final exercise
intensities were 3.6 ± 0.6 mmol/l, which showed nosignificant differences between normal and abnormal ST groups（3.6 ± 0.6 vs 3.7 ± 0.8 mmol/l）.
Table 1 shows comparisons of patient characteristics between normal and abnormal ST groups.
Serum triglyceride（p ＜ 0.01）, fasting glucose（p ＜0.01）, fasting insulin（p ＜ 0.01）, HOMA-IR（p ＜0.01）, uric acid（p ＜ 0.05）, resting systolic bloodpressure [SBP（p ＜ 0.05）] and number of the risk
factors（ p ＜ 0.05）were significantly higher andinsulin sensitivity index（p ＜ 0.01）and VO 2
max/LBM（p ＜ 0.01）were significantly lower in
the abnormal ST group than in the normal ST
group. The plasma glucose levels at 90（p ＜ 0.05）
and 120 min（p ＜ 0.01）
after oral glucose load and∑ glucose during OGTT（p ＜ 0.05）were significantly higher in the abnormal ST group than in thenormal ST group. The serum insulin levels at 60（p ＜ 0.01）, 90（p ＜ 0.05）and 120 min（p ＜ 0.01）
after oral glucose load and ∑ insulin during OGTT
（p ＜ 0.01）were also significantly higher in theabnormal ST group than in the normal ST group（Fig. 1）. The abnormal ST group showed a significantly higher prevalence of hypertension, impaired
glucose tolerance and metabolic syndrome than thenormal ST group（Fig. 2）.
For the stepwise multiple logistic regression
models, first we included age, sex, smoking habit,
triglyceride, fasting glucose, fasting insulin, uricacid, SBP and ・VO2 max/LBM as variables（Model1）, then fasting glucose [odds ratio（OR）: 1.050,
95% confidence interval（CI）: 1.001−1.101, p ＜0.05], fasting insulin（OR : 1.123, 95% CI : 1.009−
1.250, p ＜ 0.05）, uric acid（OR : 1.915, 95% CI :1.153−3.181, p ＜ 0.05）and SBP（OR : 1.041, 95%
CI : 1.001−1.082, p ＜ 0.05）were positively andsignificantly associated with ST segment depresJ Cardiol 2007 May; 49（5）: 231 – 239

ST Segment Depression and Insulin Resistance235

Fig. 2 Comparison of prevalence of coronary risk factors（■:abnormal, □:normal）
between thenormal and abnormal ST groups
Metabolic syndrome was defined according to the metabolic syndrome diagnostic criteria in Japan.14）
Abbreviation as in Table 1.

sion in exercise ECG. Next, we included ∑ insulin
during OGTT
（Model 2）, HOMA-IR（Model 3）andinsulin sensitivity index（Model 4）in place of fasting insulin. In the model 2, fasting glucose（OR :1.055, 95% CI : 1.005−1.108, p ＜ 0.05）, Σ insulin（OR : 1.013, 95% CI : 1.002−1.025, p ＜ 0.05）,
uric acid（OR : 1877, 95% CI : 1.132−3.115, p ＜0.05）and SBP（OR : 1.041, 95% CI : 1.001−1.082,
p ＜ 0.05）
were positively and significantly associated with ST segment depression in exercise ECG.
HOMA-IR（OR : 1.482, 95% CI : 1.048−2.219,
p ＜ 0.05）
as well as uric acid（OR : 1.910, 95% CI :1.157−3.154, p ＜ 0.05）
and SBP（OR : 1.041, 95%
CI : 1.001−1.082, p ＜ 0.05）in Model 3 and insulin
sensitivity index（ OR : 0.694, 95% CI : 0.497−
0.968, p ＜ 0.05）, uric acid（OR : 1.857, 95% CI :and SBP（OR : 1.041, 95%
1.107−3.115, p ＜ 0.05）
CI : 1.001−1.084, p ＜ 0.05）
in Model 4 were positively associated with ST segment depression. In an
J Cardiol 2007 May; 49（5）: 231 – 239

additional model, after excluding for the indices of
insulin resistance（Model 5）, fasting glucose（OR :1.045, 95% CI : 0.998−1.095, p ＜ 0.05）, uric acid
（OR : 1.842, 95% CI : 1.131−3.001, p ＜ 0.05）,
SBP（OR : 1.040, 95% CI : 1.001−1.080, p ＜ 0.05）
and ・
VO2 max/LBM（OR : 0.862, 95% CI : 0.758−
0.980, p ＜ 0.05）were positively and significantly
associated with ST segment depression（Table 2）.
There were no significant associations regarding
age, sex, smoking habit and ST segment depression
at the final exercise intensities in all models.
DISCUSSION
This study was performed in a limited populationof obese subjects with coronary risk factors who
were recruited to participate in our exercise therapy
program for intervention in their risk factors. Prior
to exercise therapy, we performed the exercise
stress test to evaluate myocardial ischemia. As a

236

Michishita, Shono, Kiyonaga et al

Table 2

Association between exercise-induced ST segment depression and risk factors for coronary heart disease by
stepwise multiple logistic regression analysis

Age
Sex
Smoking habit
Triglyceride
Fasting glucose

Fasting insulin

Model 1Model 2

0.960

0.955

（0.916−1.006） （0.912−1.003）
0.379

0.412

（0.076−1.885） （0.082−2.071）
1.153

0.931

（0.258−5.148） （0.210−4.119）
1.005

1.005

（0.996−1.014） （0.996−1.013）
1.050＊

1.055＊（1.001−1.101） （1.005−1.108）
1.123＊（1.009−1.250）−
1.013＊

Σinsulin−

HOMA-IR−−

Insulin sensitivity index−−

Uric acid
SBP・VO2max/LBM

Number of risk factors（1.002−1.025）

1.877＊
1.915＊（1.153−3.181） （1.132−3.115）
1.041＊
1.041＊（1.001−1.082） （1.001−1.082）
0.895

0.881

（0.784−1.022） （0.768−1.011）
0.543

0.562

（0.274−1.075） （0.286−1.105）

Model 3Model 4Model 5

0.957

0.962

0.9579（0.914−1.002）（0.918−1.009）（0.906−1.004）

0.373

0.404

0.358

（0.076−2.148）（0.073−1.751）（0.076−1.826）
1.139

1.449

0.901

（0.260−4.994）（0.301−6.975）（0.220−3.682）

1.005

1.004

1.006

（0.996−1.014）（0.995−1.012）（0.997−1.015）

1.036

1.037

1.045＊（0.989−1.086）（0.987−1.090）（0.998−1.095）

−

−

−

−

−

−

−

−

1.482＊（1.048−2.219）−

0.694＊（0.497−0.968）−

1.910＊

1.857＊

1.842＊（1.157−3.154）（1.107−3.115）（1.131−3.001）

1.041＊

1.041＊

1.040＊（1.001−1.082）
0.889（1.001−1.084）
0.905（1.001−1.080）（0.779−1.013）
0.551（0.789−1.034）
0.535（0.758−0.980）
0.618（0.279−1.088）（0.270−1.060）（0.323−1.184）

0.862＊The results are shown as the odds ratio（95% confidence interval）.＊p＜0.05.
Logistic regression used age, sex, smoking habit, triglyceride, fasting glucose, fasting insulin, uric acid, SBP, ・VO2max/LBM andnumber of the risk factors as continuous variables（Model 1）. Other models used Σ insulin during the oral glucose tolerance test
（Model 2）, HOMA-IR（Model 3）
and insulin sensitivity index（Model 4）instead of fasting insulin as a continuous variable. An
additional model excluded the indices of insulin resistance, age, sex, smoking habit, triglyceride, fasting glucose, uric acid, SBP,・VO2max/LBM and number of the risk factors as continuous variables（Model 5）.
Abbreviations as in Table 1.

result, silent ST segment depression during exercise
testing was observed in 27/114 patients（23.7%）.
The abnormal ST group showed higher fasting
insulin level, ∑ insulin during OGTT, HOMA-IR
and lower insulin sensitivity index than the normal
ST group. In addition, our multiple logistic regression analysis showed that these insulin resistanceindices were more powerfully associated with ST
segment depression, compared to other risk factors.
Several studies have reported an association
between abnormal ST-T in the resting ECG and
insulin resistance.9−11）Marita et al.9）and Sheu etal.10）observed the insulin response during OGTT
in hypertensive patients with abnormal ST-T to behigher than that in hypertensive patients withoutabnormal ST-T as well as that in normotensive subjects. Adachi et al.11）also reported that the plasma
insulin level was related to the incidence of ST-T
abnormalities in resting ECG and that the bloodpressure or other risk factors had little effect on the
ST-T abnormalities. In a recent study, Gazzaruso etal.18）showed an independent association of metabolic syndrome and insulin resistance with silent
myocardial ischemia in patients with type 2 diaJ Cardiol 2007 May; 49（5）: 231 – 239

ST Segment Depression and Insulin Resistancebetes mellitus. We also observed that the abnormal
ST group showed significantly higher prevalencesof hypertension, impaired glucose tolerance andmetabolic syndrome than the normal ST group, andour findings support the recent results from
Gazzaruso et al. At present, the mechanisms
regarding the association between exercise-induced
ST segment depression and insulin resistance are
not well known. Although none of our 27 patientswith abnormal ST underwent coronary angiography, some of them might possibly have had occult
atherosclerotic large coronary artery disease. On
the other hand, abnormal glucose metabolism isconsidered to be associated with micro-vessel coronary artery disease,19）which might cause ST abnormality in some patients. However, it is also possiblethat insulin resistance was correlated with a falsepositive exercise ECG response for coronary heartdisease that might in part be caused by cardiac
metabolic abnormalities. In our study, final exercise
intensity was above the LT in all patients. Insulin
resistance or hyperinsulinemia induces an increasein plasma catecholamine concentration.20,21）The
plasma catecholamine concentration increased
exponentially above the LT during the exercise test,
and the plasma catecholamine threshold was significantly correlated to LT. 22）Insulin resistance or
hyperinsulinemia promotes the release of plasma
endothelin levels from vascular smooth muscle
cells.23）Plasma endothelin levels increase during
exercise, due to an increased exercise intensity.24）
In addition, insulin is thought to promote the proliferation of cardiac myocytes.25）Therefore, the association between ST segment depression in exercise
ECG and insulin resistance might be caused by asympathetic nervous system activity above the LT
or cardiac hypertrophy.
In our data, not only the insulin resistanceindices, but also other risk factors were related toexercise-induced ST segment depression. The ST
segment depression was also correlated with fasting
glucose, SBP, uric acid and ・VO2 max/LBM after
excluding for the indices of insulin resistance.
Associations between ST segment depression andplasma glucose and blood pressure9−11）level havebeen reported. Katzel et al.26）observed that exercise-induced silent myocardial ischemia, and lower
・VO2 max levels and sedentary lifestyle were independent predictors of cardiac events in healthy,
sedentary, obese, middle-aged and older men. Our
results might support the findings of these studies.
J Cardiol 2007 May; 49（5）: 231 – 239

237

There have been several reports indicating an association between ST segment depression and uricacid. Adachi et al.11）reported that subjects withabnormal ST-T in resting ECG showed significantly
higher levels of uric acid than subjects with normal
ST-T. Uric acid might be an independent risk factor
for cardiovascular disease. 27,28）The mechanism
regarding the relationship between exerciseinduced ST segment depression and uric acid might
be related to the fact that increased sympathetic
nervous system activity induces decreased uric acidexcretion.29）Increased risk factors for cardiovascular disease and decreased vasodilator action, i.e.
decreased vascular nitric oxide production andnitric oxide activity,30）are correlated with uric acidelevation. As a result, not only insulin resistance,but other factors such as hyperglycemia, hyperuricemia, hypertension and lower aerobic capacity
may also be involved in the pathological ST depression during exercise.
Study limitation and clinical implication
There are several limitations in this study. First,
our limited study population combined small numbers of subjects and middle-aged females predominanted. Second, our evaluation of ST segment
depression was performed using only the CM5-lead.
Third, the presence of myocardial ischemia, left
ventricular hypertrophy and mitral valve prolapse,
abnormality in wall motion, wall thickness andvalvular activity, which also affect exercise-induced
ST segment depression, could not be determined in
the 27 patients with ST segment depression.
Modalities such as coronary angiography, nuclear
myocardial perfusion imaging or echocardiography
are needed. Finally, insulin sensitivity index was
evaluated by a less sensitive method than the euglycemic hyperinsulinemic clamp and minimalmodel technique. However, Mark et al.31）reported
that silent ST segment depression during exercise
alone could predict the long term prognosis.
Therefore, our findings of the linkage between
insulin resistance and exercise-induced ST segment
depression may support the hypothesis that insulin
resistance leads to future cardiovascular events.
There have been several studies32）on the effectof exercise therapy for improving insulin resistance.
However, whether exercise therapy improves theexercise-induced ST segment depression in association with the reduction in serum insulin levels
remains unknown, so further research is required.

238

Michishita, Shono, Kiyonaga et al

Since exercise-induced ST segment depression is apredictor of long term prognosis, evaluation should
be recommended prior to exercise therapy in obese
subjects with insulin resistance.

cise, as well as with the previously reported factors
such as hyperglycemia, hyperuricemia, hypertension and lower aerobic capacity.
Notice of grant support

CONCLUSIONSThis study was supported in part by a grant from the Japanese

These results suggest that insulin resistance may
involve the pathological ST depression during exer-

Ministry of Education（No.16500445）.

要

約

肥満者の運動負荷心電図 ST 下降とインスリン抵抗性との関係
道下

目

竜馬

庄野菜穂子

清 永

明

田中

宏暁

進藤

笠原

貴紀

敏幸

井上

晃男

野出

孝一

鶴田

宗洋

的 : インスリン抵抗性は虚血性心疾患の独立した危険因子であり，安静時心電図 ST 低下の発症とも関与することが報告されている．しかし，運動負荷心電図 ST 下降とインスリン抵抗性との関係については明らかにされていない．本研究では肥満者を対象に運動負荷心電図 ST 下降とイ
ンスリン抵抗性との関係について検討した．
方

法 : 冠危険因子を有する肥満者 114 例（男性 39 例，女性 75 例，平均年齢 50.9 ± 12.2 歳，平均

体格指数 28.6 ± 3.1 kg/m2）を対象に，自転車エルゴメーターを用いて 4 分ごとに 5−10 W 漸増する
最大下多段階運動負荷試験を施行した．心電図は CM5 誘導により安静時より運動終了後まで連続して記録した．
結果 : 最大運動負荷時に ST 下降が認められた群（ST 下降群）は，中性脂肪，インスリン抵抗性指数（HOMA-IR），血清尿酸値，収縮期血圧，空腹時ならびに糖負荷試験（OGTT）中の血糖，インスリンの各値が ST 下降のなかった群（正常 ST 群）に比べて有意に高かった．また，ST 下降群は，インスリン感受性指数，最大酸素摂取量（・VO max）が正常 ST 群に比べて有意に低かった．ロジス
2

ティック回帰分析を用い，年齢，性別，喫煙習慣，中性脂肪，血清尿酸値，収縮期血圧，・
VO2 max，
空腹時血糖，空腹時インスリンを連続変数として ST 下降に対する相対危険度を検討したところ，
空腹時インスリンは ST 下降と有意に相関し，HOMA-IR，Σインスリン，インスリン感受性指数を空腹時インスリンの代わりとした場合も同様に相関が認められた．また，インスリンの影響を除外して ST 下降に対する相対危険度を検討したところ，空腹時血糖，収縮期血圧，血清尿酸値，・
VO max2に有意な相関関係を認めた．
結論 : インスリン抵抗性は ST 下降の発症に関与し，運動負荷心電図 ST 下降の予測因子である

可能性が示唆された．

J Cardiol 2007 May; 49（5）: 231−239

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